Clinical characteristics and management of orbital apex syndrome: a 10-year multicentre experience.

BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

The impact of dermatological toxicities of anti-cancer therapy on the dermatological quality of life of cancer patients.

BACKGROUND: One of the most common side effects of anti-cancer therapies is treatment-induced skin changes, referred to as dermatological toxicities. These dermatological toxicities are noteworthy since they have a negative association with quality of life (QoL). OBJECTIVES: To evaluate the impact of dermatological toxicities on QoL of cancer patients and to identify the relationship between disease-related characteristics and QoL and changes in skin protective behaviours following anti-cancer therapy. METHODS: Cancer patients (n = 80: stage II-IV) in a longitudinal prospective study completed a battery of questionnaires at the time of enrolment and after 3 months of anti-cancer therapy. QoL, skin toxicities, smoking and drinking behaviour, sun-protective and skin care behaviour assessments were performed before and at 3 months after anti-cancer therapy. QoL was measured with the Dermatology Life Quality Index (DLQI). RESULTS: A total of 73 patients completed the study. Among them, 48 patients (65.8%) experienced at least grade 1 skin toxicity at 3 months after anti-cancer therapy. Hair loss, hyperpigmentation and dry skin were the most common dermatological toxicities. The mean baseline DLQI score changed from 1.38 to 3.49 at 3 months after anti-cancer therapy. Domain 1 (symptoms and feelings, 1.38 points) was the most greatly impacted among patients by anti-cancer treatment. Patients who experienced at least grade 1 skin toxicity (P = 0.001, 95% CI: 1.939-4.899), employed (P = 0.042, 95% CI: 0.030-1.476), more highly educated (P = 0.030, 95% CI: 0.161-3.132), and diagnosed with gastric cancer (P = 0.001, 95% CI: 2.141-8.250) or renal cell cancer (P = 0.002, 95% CI: 2.731-11.364) showed significantly higher DLQI scores. Patients showed significant change in skin protective behaviour such as use of body moisturizer (P = 0.021) and change in drinking behaviour (P = 0.006) at 3 months following anti-cancer therapy. CONCLUSION: Dermatological toxicities due to anti-cancer therapy affect the QoL of cancer patients. Therefore, health care professionals should pay attention to the psychological effects of skin problems and educate cancer patients to adapt proactive skin protective behaviours to minimize dermatological toxicities of anti-cancer therapy and maximize QoL.

Increased interstitial pressure improves nucleic acid delivery to skin enabling a comparative analysis of constitutive promoters.

Nucleic acid-based therapies hold great promise for treatment of skin disorders if delivery challenges can be overcome. To investigate one mechanism of nucleic acid delivery to keratinocytes, a fixed mass of expression plasmid was intradermally injected into mouse footpads in different volumes, and reporter expression was monitored by intravital imaging or skin sectioning. Reporter gene expression increased with higher delivery volumes, suggesting that pressure drives nucleic acid uptake into cells after intradermal injections similar to previously published studies for muscle and liver. For spatiotemporal analysis of reporter gene expression, a dual-axis confocal (DAC) fluorescence microscope was used for intravital imaging following intradermal injections. Individual keratinocytes expressing hMGFP were readily visualized in vivo and initially appeared to preferentially express in the stratum granulosum and subsequently migrate to the stratum corneum over time. Fluorescence microscopy of frozen skin sections confirmed the patterns observed by intravital imaging. Intravital imaging with the DAC microscope is a noninvasive method for probing spatiotemporal control of gene expression and should facilitate development and testing of new nucleic acid delivery technologies.

The effect of grain boundaries inside the individual ZnO nanowires in gas sensing.

We present the gas sensing characteristics of the individual ZnO nanowires with single-crystalline and multiple grain boundaries (GBs) fabricated using bottom-up and top-down approaches, respectively. The sensor response of the individual ZnO nanowires with the multiple GBs was enhanced approximately three times as compared to that of single-crystalline ZnO nanowires due to well-known GB modulations. However, the response and recovery times of the individual ZnO nanowires with multiple GBs were much slower than those of the single-crystalline ZnO nanowire, indicating the presence of oxygen diffusion resistance to GBs due to the relatively fast surface kinetic reaction. Simplified kinetic diffusion modeling and experimental results could quantify the significant diffusion resistance of gas molecules into the GBs of the individual ZnO nanowires.

The synthesis of single PdAu bimetallic nanowire: feasibility study for hydrogen sensing.

Single PdAu bimetallic nanowires have been synthesized via the sequential processes of electrochemical deposition and dielectrophoresis (DEP). In the first step, Pd/Au grains on predefined Au electrodes were grown by electrochemical deposition and could assist effectively the formation of a single PdAu nanowire with a good directionality by the subsequent DEP process. The synthesized PdAu nanowires have an average of approximately 10 at.% of Pd, a good resistance of a few hundred Omega, diameters of 300 nm on average and lengths of up to 15 microm. Based on the single PdAu nanowire, hydrogen detection was demonstrated in the range from 100 to 2500 ppm.

siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model.

Small interfering RNAs (siRNAs) can be designed to specifically and potently target and silence a mutant allele, with little or no effect on the corresponding wild-type allele expression, presenting an opportunity for therapeutic intervention. Although several siRNAs have entered clinical trials, the development of siRNA therapeutics as a new drug class will require the development of improved delivery technologies. In this study, a reporter mouse model (transgenic click beetle luciferase/humanized monster green fluorescent protein) was developed to enable the study of siRNA delivery to skin; in this transgenic mouse, green fluorescent protein reporter gene expression is confined to the epidermis. Intradermal injection of siRNAs targeting the reporter gene resulted in marked reduction of green fluorescent protein expression in the localized treatment areas as measured by histology, real-time quantitative polymerase chain reaction and intravital imaging using a dual-axes confocal fluorescence microscope. These results indicate that this transgenic mouse skin model, coupled with in vivo imaging, will be useful for development of efficient and 'patient-friendly' siRNA delivery techniques and should facilitate the translation of siRNA-based therapeutics to the clinic for treatment of skin disorders.

Effects of season and low-level air pollution on physiology and element content of lichens from the U.S. Pacific Northwest.

Lichens were collected from three low-elevation sites in the western Cascade Range: HJ Andrews, OR (clean) and Bull Run, OR, and Pack Forest, WA (moderately enhanced nitrogen and sulfur deposition). The latter sites were within 50 km of Portland and Seattle/Centralia urban-industrial areas, respectively. Tissue concentrations of sulfur, nitrogen, and other macronutrients; rates of net carbon uptake; concentrations of photosynthetic pigments; and thallus density were correlated with season and seasonal changes in Platismatia glauca. Ion concentrations in precipitation and total wet deposition were measured from natural settings. Concentrations of depositional ions in precipitation, including NO3- and NH4+, were generally highest at Bull Run and Pack Forest; SO4(2-) concentrations and acidity were highest at Pack Forest. Total wet deposition was higher in the winter rainy season than the dry summer season at all three sites. Lichens adapted physiologically and morphologically to the higher light intensity and the warm, dry climate of summer through decreased optimal water content for CO2 uptake, increased concentrations of carotenoids and increased thallus density. Compared to the clean site, the sites with enhanced deposition were associated in P. glauca with year-round higher tissue concentrations of N, S, K, and Na; higher concentrations of total chlorophyll and carotenoids; higher OD435/415 ratios; higher CO2 uptake and lower thallus density in summer; and a general absence of other sensitive lichens. These results indicate that moderate levels of fertilizing air pollutants can stimulate carbon uptake and provide protection against chlorophyll degradation in air pollution-tolerant lichens of the Pacific Northwest, especially during the dry summer season.

Antisense IL-10 abrogates the inhibitory effects of IL-10 production by transfected tumor cells.

Interleukin-10 (IL-10) is a pleiotropic cytokine that has a variety of downregulatory effects on immunologic and inflammatory processes. Ectopic tumor expression of IL-10 inhibited tumor growth, and local administration of antisense IL-10 significantly reversed the effects of IL-10 transfection in P815 mastocytoma. Tissue inhibitors of metalloproteinase (TIMPs) have been associated with decreased tumorigenesis and reduced metastasis, and TIMPs were increased in the region surrounding P815/IL-10 tumors and reduced in antisense IL-10-treated mice. In addition, the antisense IL-10 group had the largest tumor volume and poorest survival when compared with the P815/IL-10 control or sense groups. In summary, our data suggest that, in a mouse model, antisense IL-10 has substantive effects in reducing IL-10 translation and inhibiting IL-10-mediated TIMP upregulation, and, by doing so, allows IL-10-transfected mastocytoma to grow unchecked. Thus, ectopic tumor expression of IL-10 inhibits tumor growth, and antisense IL-10 administration in vivo reverses this protective effect.

Muscle cell peeling from micropatterned collagen: direct probing of focal and molecular properties of matrix adhesion.

To quantitatively elucidate attributes of myocyte-matrix adhesion, muscle cells were controllably peeled from narrow strips of collagen-coated glass. Initial growth of primary quail myoblasts on collagen strips was followed by cell alignment, elongation and end-on fusion between neighbors. This geometric influence on differentiation minimized lateral cell contact and cell branching, enabling detailed study of myocyte-matrix adhesion. A micropipette was used to pull back one end of a quasi-cylindrical cell while observing in detail the non-equilibrium detachment process. Peeling velocities fluctuated as focal roughness, microm in scale, was encountered along the detachment front. Nonetheless, mean peeling velocity ( microm/second) generally increased with detachment force (nN), consistent with forced disruption of adhesion bonds. Immunofluorescence of beta1-integrins correlated with the focal roughness and appeared to be clustered in axially extended focal contacts. In addition, the peeling forces and rates were found to be moderately well described by a dynamical peeling model for receptor-based adhesion (Dembo, M., Torney, D. C., Saxman, K. and Hammer, D. (1988). Proc. R. Soc. Lond. B 234, 55-83). Estimates were thereby obtained for the spontaneous, molecular off-rate (kooff, (less than or equal to)10/seconds) and the receptor complex stiffness (kappa, approx. 10(-5)-10(-6) N/m) of adherent myocytes. Interestingly, the local stiffness is within the range of flexible proteins of the spectrin superfamily. The overall approach lends itself to elucidating the developing function of other structural and adhesive components of cells, particularly skeletal muscle cells with specialized components, such as the spectrin-homolog dystrophin and its membrane-linked receptor dystroglycan.

[An investigation of X-ray examinations classified according to cases of dental diseases at Fukuoka Dental College Hospital].

This paper reports the results of an investigation on the types and frequencies of X-ray examinations given to patients with various types of their dental diseases from their first visit to the hospital to the end of treatment. The subjects were 337 patients (not including orthodontic patients and in-patients) randomly sampled out of all those who visited the Fukuoka Dental College Hospital in 1986. Out of these 337, the number of those who were given X-ray examinations was 284. 1. The Cases of dental diseases for which X-ray examinations were given were classified into the following seven: diseases caused by dental caries, trauma, inflammation, diseases of temporomandibular joint, diseases of salivary gland and other diseases, and other examinations. Out of these X-ray examinations, those given to the patients of diseases caused by dental caries and marginal periodontitis amounted to the 60% of the total X-ray examinations. 2. On the average, 3.3 radiographs were taken per patient. 3. In the examination of luxation, a case of trauma, 7.8 radiographs were taken per patient, the largest number of all diseases on this report. In the examination of marginal periodontitis, a case of inflammation, 5.4 dental radiographs and 0.5 panoramic radiograph were taken per patient. It is necessary to make the most of panoramic examination effective for this disease to decrease radiation exposure. 4. The diseases that have more difficulty of diagnosis and more necessity of observing the prognosis had a greater tendency to depend on X-ray examinations. 5. The percentage of the patients who did not receive X-ray examination was 15.7%. Out of these patients, the patients in pedodontics accounted for 34.5%.